microRNA expression pattern and its alteration following celecoxib intervention in human colorectal cancer

Abstract

Accumulating evidence suggests that aberrant expression of microRNAs (miRNAs) is involved in several diseases, including cancer. This study aimed to investigate the miRNA expression pattern and its alteration following celecoxib intervention for human colorectal cancer (CRC). The miRNA expression profiles of CRC tissues, matched adjacent normal colorectal mucosae and HT-29 cells treated with celecoxib were determined using miRNA microarray, and further confirmed using the quantitative reverse transcription-- polymerase chain reaction (Q-RT-PCR). The target genes of the aberrant miRNAs in HT-29 cells treated with celecoxib were further assessed through bioinformatic analysis. Results from this study demonstrated a significant increase in the expression of 35 miRNAs and a decrease in 30 miRNAs in the carcinoma tissues compared to the normal tissues (P<0.001). Of the 28 aberrantly expressed miRNAs, 20 were upregulated and 8 were downregulated in the HT-29 cells treated with celecoxib compared to the matched control cells (P<0.01). Furthermore, miR-552 was found to be correlated with clinical stage, lymph node and distant metastases (P<0.05). Stage and distant metastases revealed differential expression of miR--139-3p and grade disclosed aberrant expression of miR-142-3p. In addition, multiple target genes involved in several essential survival pathways were found be modulated by the aberrantly expressed miRNAs in HT-29 cells treated with celecoxib. Our data revealed that a common pattern of miRNA expression in the colorectum could distinguish malignant tissue from normal mucosa. Celecoxib inhibited HT-29 cell growth in vitro which was partly attributable to the altered expression of miRNAs. miRNAs may be involved in CRC tumorigenesis and can serve as potential therapeutic targets.